Engineering scalable collecting duct networks for functional kidney tissue

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PROJECT SUMMARY / ABSTRACT The proposal outlines an integrated research and career development plan for Kayla Wolf, PhD, to complete postdoctoral training under the mentorship of sponsor Jennifer Lewis, ScD, and co-sponsor Lisa Satlin, MD. The overarching goal of the proposed project to develop a functional collecting duct network that is derived from human pluripotent stem cells and interconnected with a single drainage outlet. This network could serve as a model system for hypothesis testing, disease modeling, and drug screening or could interconnect directly with nephron-rich organoids to facilitate filtrate drainage in 3D kidney tissues. Recognizing that the extracellular matrix (ECM) plays a crucial role in development, this proposal with both investigate the role of ECM in collecting duct differentiation and leverage biomaterials as a powerful tool for guiding tissue form and function. Development of the collecting duct system will be accomplished by the completion of three aims. First, ureteric bud cells (UB, collecting duct precursors) generated from emerging differentiation protocols will be validated, and the effects of adapting the protocol to scalable culture methods on UB phenotype will be tested. Second, the role of extracellular matrix (ECM) composition on UB morphological and functional differentiation will be determined. Finally, the effects of fabricating a drainage outlet in a branching UB network on transport protein expression and function will be determined. Successful completion of this proposal will elucidate the role of ECM in driving collecting duct development, advance biofabrication methodology, and produce critically needed engineering solutions for generating functional kidney tissue. Dr. Wolf (PI) was supported by an NIH F31 fellowship (F31 CA228317-01) during her graduate research, where she established expertise in biomaterials, bioengineering, and mechanobiology. Under NIH F32 support, the PI receive extensive training in biofabrication and renal physiology at Harvard University, which cultivates a well- established, globally-leading biomedical research environment. The career development plan is designed to equip the PI with the necessary knowledge and skills for a successful career as an independent academic researcher.